Reactive oxygen species (ROS) are generated in cells either by aerobic metabolism or by exposure to ionizing radiation and other oxidizing agents. They can damage cellular components by a radical-mediated mechanism. The resulting damaged products of nucleic acids have been implicated in cancer, neurological disorder, and natural processes of aging. Here we propose to develop sensitive mass spectrometric methods to characterize the structures and to quantify the amounts of oxidative DNA and RNA lesions, and there is a strong prospect that we will find new lesions. We also propose to study the chemical and biological properties of those oxidative lesions via mass spectrometry. Molecular modeling, organic synthesis, and other spectroscopic techniques will also be employed to answer those questions. The outcome of the research proposed here will provide better understanding of the biological consequences of oxidative damage on nucleic acids by ROS and their implications in human health.